Abstract
Therapeutic hypothermia (HT) is frequently used in neonates with hypoxic-ischemic encephalopathy and young infants during cardiopulmonary bypass (CPB). Hypothermia and CPB result in physiological changes contributing to pharmacokinetic (PK) and pharmacodynamic (PD) changes. Changes in the absorption, the volume of distribution (Vd) and the total body clearance (CL) of drugs used during hypothermia and CPB might lead to the interindividual PK variability resulting in either insufficient or toxic plasma concentrations and have an impact on the biodisposition and action of drugs. Both under- or overdosing of medicines in these critically ill patients may contribute to a worse overall outcome. Overall, hypothermia decreases CL but may decrease or increase Vd by changing intravascular blood volume, organ perfusion and enzymatic metabolic processes. In addition, maturational as well as organ specific changes may occur during hypothermia superimposed on the underlying disease and/or procedures such as extracorporeal membrane oxygenation (ECMO) or CPB. This paper will provide an overview of variables and potential covariates (e.g., asphyxia, sepsis, multiorgan dysfunction syndrome, cardiac arrest) determining the PK of frequently used drugs. In addition, the effects of hypothermia on individual drugs are described as well as alternative ways for future study designs such as the use of population PK-PD and opportunistic sampling. Ultimately, these investigations are warranted to obtain specific dosing nomograms of medicines for use in clinical practice and to improve the treatment results of this vulnerable group of pediatric patients.
Keywords: Hypothermia, pharmacokinetics, pharmacodynamics, pharmacogenomics, developmental pharmacology, absorption, distribution, metabolism, and excretion, neonates, infants, covariates, asphyxia, sepsis, multiorgan dysfunction syndrome, cardiac arrest.
Current Pharmaceutical Design
Title:The Impact of Hypothermia on the Pharmacokinetics of Drugs Used in Neonates and Young Infants
Volume: 21 Issue: 39
Author(s): P. Pokorna, E.D. Wildschut, V. Vobruba, John N. van den Anker and D. Tibboel
Affiliation:
Keywords: Hypothermia, pharmacokinetics, pharmacodynamics, pharmacogenomics, developmental pharmacology, absorption, distribution, metabolism, and excretion, neonates, infants, covariates, asphyxia, sepsis, multiorgan dysfunction syndrome, cardiac arrest.
Abstract: Therapeutic hypothermia (HT) is frequently used in neonates with hypoxic-ischemic encephalopathy and young infants during cardiopulmonary bypass (CPB). Hypothermia and CPB result in physiological changes contributing to pharmacokinetic (PK) and pharmacodynamic (PD) changes. Changes in the absorption, the volume of distribution (Vd) and the total body clearance (CL) of drugs used during hypothermia and CPB might lead to the interindividual PK variability resulting in either insufficient or toxic plasma concentrations and have an impact on the biodisposition and action of drugs. Both under- or overdosing of medicines in these critically ill patients may contribute to a worse overall outcome. Overall, hypothermia decreases CL but may decrease or increase Vd by changing intravascular blood volume, organ perfusion and enzymatic metabolic processes. In addition, maturational as well as organ specific changes may occur during hypothermia superimposed on the underlying disease and/or procedures such as extracorporeal membrane oxygenation (ECMO) or CPB. This paper will provide an overview of variables and potential covariates (e.g., asphyxia, sepsis, multiorgan dysfunction syndrome, cardiac arrest) determining the PK of frequently used drugs. In addition, the effects of hypothermia on individual drugs are described as well as alternative ways for future study designs such as the use of population PK-PD and opportunistic sampling. Ultimately, these investigations are warranted to obtain specific dosing nomograms of medicines for use in clinical practice and to improve the treatment results of this vulnerable group of pediatric patients.
Export Options
About this article
Cite this article as:
Pokorna P., Wildschut E.D., Vobruba V., van den Anker N. John and Tibboel D., The Impact of Hypothermia on the Pharmacokinetics of Drugs Used in Neonates and Young Infants, Current Pharmaceutical Design 2015; 21 (39) . https://dx.doi.org/10.2174/1381612821666150901110929
DOI https://dx.doi.org/10.2174/1381612821666150901110929 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Therapeutic microRNA Delivery Strategies with Special Emphasis on Cancer Therapy and Tumorigenesis: Current Trends and Future Challenges
Current Drug Metabolism Cardioprotector Activity of an Esteroidal Saponin: A Scientific and Technological Prospection
Recent Patents on Biotechnology Advances in Liver-Directed Gene Therapy for Hepatocellular Carcinoma by Non-Viral Delivery Systems
Current Gene Therapy Chronic Thromboembolic Pulmonary Hypertension-Therapeutic Options
Current Respiratory Medicine Reviews Natural Naphthoquinones with Great Importance in Medicinal Chemistry
Current Organic Synthesis Inflammatory Mediators and the Failing Heart: A Translational Approach
Current Molecular Medicine Parvovirus B19 (B19V) Infection and Pregnancy
Current Pediatric Reviews Fibrinogen: A Predictor of Vascular Disease
Current Pharmaceutical Design Management of Obesity in Pregnancy
Current Women`s Health Reviews Drug Interactions with Angiotensin Receptor Blockers: Role of Human Cytochromes P450
Current Drug Metabolism Screening Haemostasis – Looking for Global Assays: The Overall Haemostasis Potential (OHP) Method – A Possible Tool for Laboratory Investigation of Global Haemostasis in Both Hypo- and Hypercoagulable Conditions
Current Vascular Pharmacology Prodigiosins as Anti Cancer Agents: Living Upto Their Name
Current Pharmaceutical Design Selective Peroxisome Proliferator-Activated Receptor-γ Modulation to Reduce Cardiovascular Risk in Patients with Insulin Resistance
Recent Patents on Cardiovascular Drug Discovery Evidence for the Involvement of Lamins in Aging
Current Aging Science Nutlin-3, A p53-Mdm2 Antagonist for Nasopharyngeal Carcinoma Treatment
Mini-Reviews in Medicinal Chemistry Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA
Current Cardiology Reviews MicroRNAs and Physical Activity
MicroRNA Fluorescent Cisplatin Analogues and Cytotoxic Activity
Current Medicinal Chemistry Endothelial Function and Pathogenesis of Endothelial Dysfunction
Current Immunology Reviews (Discontinued) Myocardial ‘No-Reflow’ Prevention
Current Vascular Pharmacology